Implantable product with improved aqueous interface characteristics and methods for making and using the same

ABSTRACT

An implantable medical device including a porous membrane that is treated with a hydrophilic substance to obtain rapid optimum visualization using technology for viewing inside of a mammalian body. These technologies include ultrasound echocardiography and video imaging such as that used during laparoscopic procedures.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. patent application Ser. No.12/966,748, filed Dec. 12, 2012, which is a continuation of U.S. patentapplication Ser. No. 12/106,064, filed Apr. 18, 2008, which is adivisional of U.S. patent application Ser. No. 11/051,299, filed Feb. 4,2005, now abandoned, which is a continuation of U.S. patent applicationSer. No. 10/159,836 filed May 31, 2002, now abandoned.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to implantable medical devices and moreparticularly to medical devices that are designed to be surgically orendoluminally placed in a body.

2. Description of Related Art

Medical devices designed to be introduced through catheter-baseddelivery systems or through trocars are often deployed using variousremote visualization techniques, such as x-ray imaging, fluoroscopy,ultrasound, and/or video imaging.

It has been determined that devices made from certain microporouspolymers, such as expanded polytetrafluoroethylene (PTFE), sometimes aredifficult to properly visualize using certain remote visualizationtechniques because air trapped in the microporous polymer can distortremote images. Most porous materials will eventually wet-out with bodyfluids following implantation, although this process may take time. Inthe case of expanded PTFE, its hydrophobic nature can vastly slow theprocess of replacing air with fluid following implantation—which canlead to poor initial visualization following implantation.

Expanded PTFE is now a preferred material for use with many implantablesurgical and interventional devices, such as vascular grafts,implantable sheet materials, stent-grafts, embolic filters, and variousoccluders including septal occluders. As use of this material hasincreased, it has become evident that these devices often do not provideoptimal initial visual clarity under ultrasound, video imaging, anddirect visualization.

Ultrasonic imaging is a somewhat vexing problem for implantable porousmaterials. “Sound” is generally defined as a periodic disturbance influid density, or inelastic strain of a solid, generated by a vibratingobject. In the case of “ultrasound,” it is generally defined as soundwith a frequency of over about 20,000 Hz. The velocity of ultrasoundwaves depends on the medium through which they propagate. The velocityof sound through air is about 330 m/sec; the velocity of sound throughwater is about 1480 m/sec; the velocity of sound through muscle is about1580 m/sec. While liquids tend to transmit ultrasound waves, air tendsto absorb such waves. As a result, the presence of air in an implantablemembrane introduces a disruptive layer that will interfere with normalultrasound wave transmission. While it is recognized that these problemscan be corrected by replacing the air in the porous material withliquid, this process has generally been addressed through the slowwetting-out of the porous material over time following implantation.

For some applications, this process of slow wetting-out may beundesirable. With the growing advent of remotely delivered devices, moreand more comprising a membrane attached to an expanding frame, there isa need for instantaneous exact visualization of the device prior to andimmediately following implantation. Devices such as fluoroscopes andx-rays can provide such visualization, but the harmful radiation thesedevices deliver to patients and medical personnel make them lessdesirable for daily use. Due to its very low side-effect risks,ultrasound visualization would be a preferred method of visualization,but only if the remotely deployed devices can be instantly visualizedwithout interference. To date, no entirely suitable method of instantlyultrasonically visualizing a device incorporating a porous membrane hasyet been developed.

Visualization and wet-out issues are discussed in a number of existingpatents. For instance, in Japanese Patent 10-244611 to Oga it isrecognized that expanded PTFE implantable sheet material has a number ofproblems, including that: it cannot be seen through; it reflects light,causing glare problems for surgical staff; and it cannot be effectivelyprobed with ultrasound. The patent teaches that these problems can becorrected by providing an expanded PTFE center layer that ispre-impregnated with an aqueous liquid and two outer layers sealing theliquid impregnated layer. Liquid polyvinyl alcohol (PVA) may be includedin the liquid impregnated layer. While this approach may solvevisualization problems, it presents a number of other problems,including vastly increased manufacturing, packaging, shipping, andhandling problems while dealing with a pre-wetted material.

In PCT Patent Application WO 96/40305 to Hubbard, it is again recognizedthat expanded PTFE cannot be seen through, it reflects light, and it isnot suitable for ultrasound imaging. Hubbard teaches that the expandedPTFE can be pre-impregnated with saline, polysaccharides, gums and gels,glycerol/gum xanthan, sera/lipids, or the like, and then shipped wet.Again, this concept requires increased expense and effort in dealingwith the manufacturing, packaging, and handling of a “wet” product.

Separate from visualization issues, a number of other patents suggestincorporating wet or wettable materials within implantable devices forvarious reasons of improved device performance. For instance, U.S. Pat.No. 4,193,138 to Okita teaches use of an expanded PTFE vascular graftwith a water-soluble polymer in its pores. The polymer in the poresforms a bonded film of water, preventing adsorption of plasma protein,which is claimed to improve patency. Multiple types of cross-linked PVAare disclosed as a “swollen gel” in the pores of the expanded PTFE.

Similarly, U.S. Pat. No. 5,041,225 to Norman teaches an expanded PTFEmembrane coated with a combination of a hydrophilic polymer and acomplexing agent. The polymer is rendered water insoluble by thecomplexing agent, which also provides good protein bonding. PVA istaught as the hydrophilic polymer and various inorganic compounds, suchas boric acid, sodium borate, etc., are taught as the complexing agents.

In U.S. Pat. No. 5,049,275 to Gillberg-LaForce et al., it is taught thata micro-porous membrane, such as expanded PTFE, can be changed fromhydrophobic to hydrophilic by incorporating a vinyl monomer, such asPVA, polymerized within the pores of the membrane. This patent teachesthat the membrane should be rendered hydrophilic to be used as aseparation membrane in rechargable batteries, or in blood oxygenators,in bioreactors or for use in blood dialysis, or to support a liquidmembrane, wherein a liquid which is imbibed in the pores of themicroporous membrane is the medium through which transport takes place.

In U.S. Pat. No. 4,525,374 to Vaillancourt it is taught that an expandedPTFE membrane can be coated to render it hydrophilic by treating it withtriethanolamine dodecylbenzene sulfonate and then dried. The patentteaches that the membrane should be rendered hydrophilic to maintain theexisting (inert characteristics) surface properties of hydrophobicmembrane filters and yet render these filters hydrophilic such that theycan be used for fluid filtration, particularly for pharmaceuticalprocesses.

In U.S. Pat. No. 5,755,762 to Bush it is taught that electricalconductivity can be improved by treating an expanded PTFE jacketedpacing or defibrillation lead with a wet-out agent, such as DSS, TDMAC,surfactants, or hydrogels. Likewise in U.S. Pat. No. 5,090,422 to Dahlet al., it is taught that an expanded PTFE pacing lead jacket can betreated with a “wetting agent, or surface modified” to allow wet-out andimprove initial electrical performance.

U.S. Pat. No. 5,897,955 to Drumheller et al. teaches that a PVA coatingcan be provided on an expanded PTFE surface to aid in attaching variousbiological entities. U.S. Pat. No. 5,902,745 to Butler et al. teachesthat a PVA treatment can be provided in the wall of an expanded PTFEcell containment device to aid in seeing the cells inside.

In summary, numerous concepts have been previously proposed forrendering a porous membrane wet or wettable for a number of functionalreasons. However, particularly with regard to endoscopically deployeddevices that mount porous membranes on some form of support frame, noneof these previous concepts has taught or suggested an ideal solution toaid in the instant visualization of an implanted device that is highlyeffective, simple to implement, and does not urden the manufacturing,packaging, shipping, or handling of the implantable device.

SUMMARY OF THE INVENTION

The present invention employs treatment of an implantable medicaldevice, comprising a microporous membrane supported by a frame, thatallows the device to be rapidly and accurately visualized by ultrasoundand video imaging, and renders the device transparent under directvisualization. The present invention eliminates air-interference issueswith porous membrane devices, such as those incorporating expanded PTFE,by modifying the porous membrane with a dried hydrophilic substance,such as polyvinyl alcohol (PVA), to allow the membrane to rapidlydisplace air with liquid once introduced into the body or otherwisecontacted with an aqueous liquid. The presence of dried hydrophilicsubstance on and/or in the pores of the membrane vastly increases therate at which air is displaced by aqueous liquids and improves the rapidand precise visualization of the device.

The preferred device of the present invention comprises an expandableframe attached to a porous expanded PTFE membrane that includes across-linked PVA material bound to the membrane. This construction issuitable for use with a wide variety of remotely deployed devices, suchas septal and other occlusion devices, embolic filters, certainstent-graft devices, implantable sheets, and the like. In addition toallowing for very rapid accurate visualization of the implanted device,the present invention is believed to also provide a number of otherbenefits, including improved biological performance and better ingrowth.

Another benefit of the present invention is its ability to absorbaqueous solution, which may contribute to a significant decrease in theabrasion type injuries seen when membranes come in contact with tissue.In those instances where a membrane that is impervious to fluidtransmission is required, a barrier membrane can be inserted betweenlayers of expanded PTFE, thus allowing ultrasound transmission andingrowth.

These and other benefits of the present invention will be appreciatedfrom review of the following description.

DESCRIPTION OF THE DRAWINGS

The operation of the present invention should become apparent from thefollowing description when considered in conjunction with theaccompanying drawings, in which:

FIG. 1 is a three-quarter perspective view of a septal defect closuredevice of the present invention, including a frame and a porousmembrane;

FIG. 2 is a cross-section view of a heart, including a septal defecttherein, showing initial deployment of the septal defect closure deviceof FIG. 1;

FIG. 3 is a cross-section view of the heart showing second stagedeployment of the septal defect closure device;

FIG. 4 is a cross-section view of the heart showing final deployment ofthe septal defect closure device;

FIG. 5 is an ultrasound image of a heart having been sealed with aconventional septal defect closure device, including a “shadow effect”caused by air trapped in the membrane portion of the device;

FIG. 6 is an ultrasound image of a heart having been sealed with aseptal defect closure device of the present invention, illustrating noshadow effect;

FIG. 7 is a three-quarter isometric view of an embolic filter of thepresent invention, including a frame and a porous membrane;

FIG. 8 is a three-quarter isometric view of a stent-graft of the presentinvention, including a frame and a porous membrane;

FIG. 9 is a three-quarter isometric view of the stent-graft of FIG. 8following exposure to an aqueous liquid, the membrane component havingbeen wetted-out so as to render visible the frame elements underneath;

FIG. 10 is a three-quarter isometric view of a porous implantablemembrane of the present invention;

FIG. 11 is a three-quarter isometric view of the porous implantablemembrane of FIG. 10 following initial implantation over a tissue defect,the membrane having been rendered transparent by contact with aqueousmedia at the surgical site;

FIG. 12 is a three-quarter perspective view of another embodiment of thepresent invention comprising an artificial cornea having a porousmembrane attached around a transparent lens member, said lens serving inpart as the frame supporting the porous membrane; and

FIG. 13 is a cross-section view along line 13-13 of FIG. 12.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is directed to the modification of implantabledevices that employ a porous membrane mounted on one or more frameelements so as to allow the device to be deployed remotely in a medicalprocedure. The porous membrane of the present invention is loaded with ahydrophilic substance that is dried on and/or within the membrane. Inits pre-implanted state the device of the present invention is visuallyand tactilely indistinguishable from conventional membrane and framedevices, but when exposed to an aqueous liquid the membrane portionwets-out rapidly so that the device becomes translucent or transparentto light and ultrasonic imaging.

One embodiment of the present invention is illustrated in FIG. 1. Inthis embodiment, the device comprises a septal defect closure device 20comprising a porous membrane 22 and a helical support frame 24. Thedevice is delivered to a treatment site in a body using a series ofconcentrically mounted catheter tubes 26 a and 26 b mounted on a mandrel28. This device is similar to those disclosed in U.S. Pat. Nos.5,879,366, 6,080,182, and 6,171,329, all to Shaw et al., and currentlyavailable for investigational purposes from W. L. Gore & Associates,Inc., Flagstaff, Ariz., under the trademark HELEX™.

The device illustrated in FIG. 1 differs from the devices described inthe Shaw patents and available under the HELEX trademark in that themembrane has been treated in accordance with the present invention torender it hydrophilic. When treated in the manner described in detailbelow, the septal defect closure device will rapidly absorb aqueoussolution so as to become transparent upon introduction into the bloodsystem of a patient. This modification provides a number of importantbenefits.

The process for deploying a septal defect closure device 20 of thepresent invention is illustrated in FIGS. 2 through 4. As shown, thedefect closure device 20 is guided into a heart 30 using the cathetertube 26 so as to position the device through a septal defect 32. Shownin FIG. 2, a first portion 34 of the device is then deployed on one sideof the septal defect 32 by releasing part of the frame 24 and attachedmembrane 22 from the catheter tube 26. A second portion 36 of the deviceis subsequently deployed on an opposite side of the septal defect, as isshown in FIG. 3. Once imaging assures the medical staff that the deviceis properly positioned, as is shown in FIG. 4, a final latch 38 isdeployed to lock the device in the septal defect and the catheter tube26 is removed.

Although the conventional device functions very well, its membranecomponent is constructed from a porous expanded polytetrafluoroethylene(PTFE) membrane, which is hydrophobic. As a result, the membrane maytake many days or weeks to fully absorb surrounding solution and becomevisually and sonically transparent. FIG. 5 is an ultrasonic image of aconventional septal defect closure device shown immediately followingimplantation. The image shows a distinct shadow (marked “Shadow Effect”)caused by air trapped in the membrane portion of the device. Untilwet-out occurs, this shadow effect makes it difficult to determine theprecise location of the device and the structure of surrounding tissueusing ultrasonic imaging.

FIG. 6 is an ultrasonic image of a device of the present invention ofcomparable orientation and dimensions of the device shown in FIG. 5.This device is shown as imaged by ultrasound immediately afterimplantation, but as can be seen, no shadow effect is evident in theimage. This is because the provision of a dried hydrophilic substancewithin the pores of the membrane 22 causes the membrane to rapidlywet-out once exposed to an aqueous medium, such as blood. As a result,both the device and the surrounding tissues can be clearly viewed usingultrasonic imaging almost instantaneously following implantation.

As the terms “rapid” and “rapidly” are used to describe the wet-outprocess of the present invention, they mean that most if not all of theair normally trapped in the porous structure of the membrane has beendisplaced by liquid within 30 seconds following contact with an aqueousmedium, and more preferably within 5 to 10 seconds following aqueousmedium contact. The effective evacuation of air can be confirmed in aporous expanded PTFE material once the membrane becomes translucent tovisual light.

To construct a device of the present invention, a hydrophilic layer isformed on a membrane by applying a polymeric hydrophilic surfactant,such as but not limited to polyvinyl alcohol (PVA) or polyvinylpyrrolidone (PVP), to the surface of the membrane. The hydrophilicsubstance may then be bound in place, such as through cross-linking thesurfactant to itself in situ. For a porous frame member, the hydrophiliclayer may optionally be adsorbed within the porous void spaces of theframe member as well.

When using a hydrophobic membrane, and if the polymer chosen for thehydrophilic layer dissolves in only high surface tension solvents, thehydrophobic membrane should be pre-wetted with a miscible solvent havinga low surface tension to enhance adsorption of the polymer onto themembrane. Examples of appropriate pre-wetting agents can be, but are notlimited to, isopropyl alcohol (IPA), ethanol, or methanol in aconcentration of about 25% to 100%, preferably 50% to 100%, and mostpreferably 70% to 100%. The membrane should be immersed in the misciblesolvent for about 1 second to one hour, preferably 5 seconds to fiveminutes, and most preferably for about 30 to 60 seconds.

The membrane is then immediately transferred into a solution of thepolymeric surfactant in an appropriate solvent. For example, a solutioncomprising a polymeric surfactant dissolved in a suitable solvent (suchas water), at a concentration of about 0.001% to about 99.9%, preferablyabout 0.25% to about 5%, and most preferably 1.5% to 2.5%, is initiallyadsorbed onto the surfaces and optionally into the porous spaces of aporous membrane simply by dipping the membrane in the solution for about0.05 minutes to about 24 hours, preferably 5 to 180 minutes, and mostpreferably for about 10 to 30 minutes. This treatment step permitsphysisorption of the surfactant to the surface of the membrane. Themembrane is then rinsed to wash off any excess polymeric surfactant andthen the polymeric surfactant may be cross-linked in place.

Suitable materials for the hydrophilic layer include, but are notlimited to, polyvinyl alcohol, polyethylene glycol, polypropyleneglycol, dextran, agarose, alginate, polyacrylamide, polyglycidol,poly(vinyl alcohol-co-ethylene),poly(ethyleneglycol-co-propyleneglycol), poly (vinyl acetate-co-vinylalcohol), poly(tetrafluoroethylene co-vinyl alcohol),poly(acrylonitrile-co-acrylamide), poly (acrylonitrile-co-acrylicacid-co-acrylamide), polyacrylic acid, poly-lysine, polyethyleneimine,polyvinyl pyrrolidone, polyhydroxyethylmethacrylate, and polysulfone,and their copolymers, either alone or in combination.

Preferred copolymers for formation of the hydrophilic layer arecopolymers comprising at least one moiety capable of physiochemicallyadsorbing to the membrane, at least one moiety capable of chemicalmodification with a suitable agent, and at least one moiety capable ofinteracting with high surface tension fluids. These moieties may beselected such that one moiety fulfills all of these three rolessimultaneously, fulfills two roles, or fulfills only one role.

Suitable solvents for this purpose include, but are not limited to,methanol, ethanol, isopropanol, tetrahydrofuran, trifluoroacetic acid,acetone, water, dimethyl formamide (DMF), dimethyl sulfoxide (DMSO),acetonitrile, benzene, hexane, chloroform, and supercritical carbondioxide.

The polymeric surfactant of the layer is covalently cross-linked toitself in situ using a suitable cross-linking agent to producesurface-bound planar molecules of extremely high molecular weight. Thesevery high molecular weight molecules serve to greatly reduce oreliminate the potential for desorption or migration of the surfactant.

Suitable reagents for use in cross-linking the polymeric surfactant insitu are compounds comprising at least two chemically functional groups,either homofunctional or heterofunctional, that include, but are notlimited to, aldehydes, epoxides, acyl halides, aryl halides,isocyanates, amines, anhydrides, acids, alcohols, haloacetals,arylcarbonates, thiols, esters, imides, vinyls, azides, nitros,peroxides, sulfones, and maleimides.

The reagents should be dissolved in solvents that wet the adsorbedlayer. Solvents suitable for dissolving the cross-linking reagentinclude, but are not limited to, acetone, water, alcohols,tetrahydrofuran (THF), dimethyl sulfoxide (DMSO), dimethyl formamide(DMF), benzene, acetonitrile, and dioxane. Other possible reagentsinclude, but are not limited to, free radicals, anions, cations, plasmairradiation, electron irradiation, and photon irradiation. One preferredcross-linking agent is glutaraldehyde, preferably using a catalyst ofhydrochloric acid (HCl), preferably dissolved in water. The membranewith the surfactant is then submersed into a solution of, but notlimited to, glutaraldehyde/HCl in a water concentration of about0.001%/0.001% to 99.9%/99.9%, preferably 0.1%/0.1% to 5%/5%, and mostpreferably 1%/1% to 3%/3%. The membrane should be submersed for anywherefrom 1 second to 3 hours, but preferably 1 minute to one hour, and mostpreferably 10 to 20 minutes followed by a final rinse to wash off anyexcess glutaraldehyde/HCl uncrosslinked residual.

When treated in this manner, the membrane will rapidly absorb liquid andwill render the device translucent to light and relatively transparentto sound. As such, the present invention has numerous applications forall kinds of endoluminally and surgically delivered devices, including:implantable closure devices; implantable filter devices; various graftand stent-graft devices; various implantable sheets, including sheetsthat include support frames; implantable devices with impermeablebarrier layers, and implantable devices with incorporating skirts orother elements of porous material. Examples of such other applicationsfor devices of the present invention are illustrated in FIGS. 7 through13.

FIG. 7 illustrates one form of an embolic filter device 40 of thepresent invention. In this embodiment, the device 40 includes a porousmembrane 42, having multiple macroscopic openings 44 therein, attachedto a guidewire 46 by a frame 48. By treating the porous membrane 42 inthe manner described above, the membrane will rapidly wet-out so as toallow clear ultrasonic imaging of the device 40 following deployment.Additionally, it is believed that rapid wet-out of the membrane may alsoprovide improved filtration performance for the membrane 42.

FIGS. 8 and 9 illustrate a stent-graft device 50 of the presentinvention. In this instance, the device 50 includes a frame 52,comprising a series of undulating stent elements 52 a, 52 b, 52 c, 52 d,52 e, and a membrane 54 mounted around the outside of the frame 52.Although wet-out of many blood-deployed graft elements is not desiredsince such wet-out can lead to serum leakage, for some applicationswhere such seepage is not an issue, a device of the present inventioncan be used to enhance visual and ultrasonic imaging. Even in instanceswhere serum leakage may be undesirable, the benefits of the presentinvention can still be achieved by providing a barrier layer within thedevice to resist serum leakage. As is shown in FIG. 8, prior to exposureto an aqueous medium, the membrane 54 completely obscures the frameelements 52 mounted therein. Once exposed to blood or other aqueousliquid, as is shown in FIG. 9, the membrane 54 becomes translucent oreven transparent so as to allow visualization of the frame 52 and theinterior of the device. This kind of device is believed beneficial forcertain stent-graft applications, such as carotid stenting, peripheralvascular stenting, or as a transjugular intrahepatic portacaval shunt(TIPS). This device may also be of use in the revision of the venousanastomosis of a vascular graft used for hemodialysis access, incoronary artery bypass graft revisions, or in stenting coronaryarteries. Additionally, the rapid wet-out of the membrane may alsoprovide additional benefits, such as presenting a better blood contactsurface within the device, and allowing more rapid cell ingrowth intothe device.

Still another application for the present invention comprises animplantable sheet device 56 as illustrated in FIGS. 10 and 11. In thisembodiment, the device 56 comprises a porous membrane, such as oneconstructed from expanded PTFE and commercially available from W. L.Gore & Associates, Inc., in a variety of forms such as those sold underthe trademarks GORE-TEX®, PRECLUDE®, MYCROMESH®, or DUALMESH®. Althoughall of these membranes have been engineered for different implantationapplications, each shares the common property of being constructed atleast in part from a hydrophobic porous expanded PTFE material. Thismaterial is highly light reflective and can result in some glaring whenimplanted under bright surgical light in the surgical site. This maylikewise be a problem when implanted endoscopically and the physicianmust view the surgical site through remote video imaging. For some suchapplications it is believed that allowing the membrane to be rapidlyrendered translucent or transparent, as is shown in FIG. 11, may aid thephysician in placing and anchoring the sheet in place. Additionally, asis also shown in FIG. 11, a translucent sheet 56 may also allowvisualization of underlying tissue 58 and confirmation of proper sheetplacement over areas requiring repair, such as a tissue tear 60. Again,additional benefits that a wetted-out sheet could provide may includeimproved blood or other body fluid contact, and/or improved tissueingrowth.

In instances where serum leakage is undesirable, a barrier membrane canbe placed within the device construct to prevent serum leakage. One suchdevice is available from W.L. Gore & Associates, Inc., as the GORE-TEX®ACUSEAL Cardiovascular Patch. This device comprises two layers ofexpanded PTFE and a middle barrier layer of thermoplastic fluoropolymerelastomer. This middle barrier layer can serve in part as a supportframe for the two layers of expanded PTFE. When the outer layers ofexpanded PTFE are treated with PVA, this embodiment of the invention isparticularly useful as a surgical membrane for use in carotid arteryendarterectomy repair, where it is desirable to check the patency of therepaired vessel immediately following the surgery using ultrasound.

As the term “membrane” is used herein it is intended to include anyporous material that may be incorporated into an implantable device inany suitable shape and configuration. Suitable configurationscontemplated by the present invention include sheets, tubes, fibers,rods, etc. Configurations may also include other shapes, such as thefolded-over strips of material illustrated in the septal defect closuredevice of FIG. 1. The porous material may include any of, or anycombination of, the following materials: expanded PTFE, polypropylene,polyolefin hollow fiber, polyvinylidene fluoride, PTFE, fluorinatedethylene propylene (FEP), hexafluoropropylene, polyethylene,polypropylene, polyamide (nylon), polyethyleneterephthalate,polyurethane, silicone rubber, polystyrene, polysulfone, polyester,polyhydroxyacid, polycarbonate, polyimide, polyamino acid, regeneratedcellulose, or proteins, such as silk, wool, and leather. Particularlypreferred for use with the present invention is a porous expanded PTFEmaterial, such as that employed in various medical products availablefrom W. L. Gore & Associates, Inc.

As the term “frame” is used herein it is intended to include any supportstructure that may be incorporated into or used with an implantabledevice. Suitable configurations may include defect closure frameconfigurations, any of a wide variety of stent frame configurations,filter frame configurations, occluder configurations, or any framedesigned to aid in the positioning of a porous material in a body.Suitable materials include metals, such as stainless steel, nitinol,MP35N, titanium, or other metals used in biomedical applications;plastics, such as PTFE, expanded PTFE, polypropylene, fluorinatedethylene propylene, hexafluoropropylene, polyethylene, polypropylene,nylon, polyethyleneterephthalate, polyurethane, silicone rubber,polystyrene, polysulfone, polyester, polyhydroxyacids, polycarbonate,thermoplastic fluoropolymer elastomer, or other plastics used inbiomedical applications; as well as other materials suitable for use inbiomedical applications. The frame may be internal, external or bothwith respect to the porous membrane.

Without intending to limit the present invention to the specificsdescribed hereinafter, the following examples illustrate how the presentinvention may be made and used.

Example 1 Process for Coating a Septal Occluder

A HELEX™ Septal Occluder (SO) is acquired from W. L. Gore & Associates,Inc., Flagstaff, Ariz. This device, illustrated in FIGS. 1 through 4,comprises a nitinol metal frame and a porous expanded PTFE sheet wrappedaround the metal frame.

The entire SO is immersed in 100% isopropyl alcohol for 30 seconds. TheSO is then transferred to a 2% PVA/DI Water solution for 30 minutes. TheSO is rinsed in DI water for 10 minutes and then placed in a 2%glutaraldehyde/1% hydrochloric acid-DI water solution for 15 minutes.The SO is then rinsed in DI water for 15 minutes and allowed to air dry.

This final treated SO wetted-out rapidly when exposed to an aqueoussolution, the membrane becoming completely translucent within 5 secondsafter submersion in a water bath.

Example 2 Process for Coating Stent-Graft

A VIATORR™ Stent-Graft is acquired from W. L. Gore & Associates, Inc.,Flagstaff, Ariz. This device, designed for establishing a shunt througha patient's liver in a transjugular intrahepatic portacaval shunt(T.I.P.S.) procedure, comprises a nitinol metal stent-element that ispartially covered with a tubular expanded PTFE graft element.

The stent-graft is placed in 100% IPA for 30 seconds and thenimmediately transferred into a 2% PVA/DI Water solution for 20 minutes.The stent-graft is then transferred into a DI water rinse for 15minutes. The stent-graft is then placed in the 2% glutaraldehyde/1%hydrochloric acid-DI water solution for 15 minutes. The stent-graft isthen transferred into a final DI rinse for 15 minutes.

The final stent-graft device wet out rapidly when exposed to DI water,becoming completely translucent within 5 seconds after submersion in thewater.

Example 3 Process for Coating Embolic Filter

The filtering membrane was made by laser perforating one layer of a thin(total thickness about 0.0005 cm (0.0002 in)) polytetrafluoroethylene(PTFE) membrane from W.L. Gore & Associates, Elkton, Md. A hole patternof uniform size and spacing was created. The perforated membrane wasthen folded on itself and heat-sealed using a soldering iron to create aconical shape. The conical flat pattern was then trimmed with scissors,inverted, and mounted on a tapered mandrel.

The conical filter membrane was attached to a nitinol metal frame usinga fluorinated ethylene propylene (FEP) powder coated adhesive (FEP 5101,available from E. I duPont de Nemours & Co., Wilmington, Del.) andlocalized heat application.

Following embolic filter construction, the embolic filter was placed in100% IPA for 30 seconds. The device was then immediately transferredinto a 2% PVA/DI Water solution for 20 minutes. Then the device wastransferred into a DI water rinse for 15 minutes. Following the rinse,the device was placed in a 2% glutaraldehyde/1% hydrochloric acid-DIwater solution for 15 minutes. The device was then transferred into afinal DI rinse for 15 minutes.

Without the PVA treatment the device would not pass any fluid. After PVAtreatment, the device was very effective at passing fluid while stoppingthe 100 micron and larger particles with over 98% efficiency.

Example 4 Process for Coating a Pericardial Membrane

A PRECLUDE® Pericardial Membrane (PCM) was acquired from W. L. Gore &Associates, Inc., Flagstaff, Ariz., and treated as follows. The PCM wasimmersed in IPA for 30 seconds. The PCM was immediately transferred intoa 2% PVA/DI Water solution for 30 minutes. The PCM was transferred intoa DI water rinse for 10 minutes. The PCM was placed in a 2%glutaraldehyde/1% hydrochloric acid-DI water solution for 15 minutes.

The PCM was then transferred into a final DI rinse for 15 minutes.

Example 5 Use of Pericardial Membrane in an Animal Model

The PCM made as described in Example 4, above, was implanted into ananimal model. Immediately following implant the PCM material becamevisually transparent and presented no noticeable glare.

Example 6 Use of Septal Occluder in an Animal—Visualization byUltrasound

An ultrasound machine (Sequoia C256, Acuson Corporation, Mountain View,Calif.) with an Intracardiac Probe (Acunav, Acuson Corporation, MountainView, Calif.) was used to assess the clarity of visualization of theHELEX Septal Occluder treated according to Example 1. The treated devicewas immersed in heparinized saline and then deployed into a canineacutely. The edges of the device were clearly seen. The differencesbetween the inventive device and a control are illustrated in FIGS. 5and 6 and have been previously described.

Example 7 Testing for Hydroxyl Groups

This example describes an assay by which uniformity of coverage ofdevices with cross-linked polyvinyl alcohol (PVA) can be qualitativelyassessed by visual inspection and quantitatively assessed by removal ofthe dye and spectrophotometric measurement of the dye concentration. Theassay employs a blue dye, Cibachron Blue 3GA, which binds to freehydroxyl groups that are present on the surface of immobilized PVA. Onemolecule of Cibachron Blue binds to one free hydroxyl, so one canquantify free hydroxyl availability by removal of the attached dye withstrong acid.

Binding of Cibachron Blue 3GA was accomplished using a modification ofthe method described in Hermanson, G. T., Mallia, A. K., and Smith, P.K., Immobilized Affinity Ligand Techniques, 1992, Academic Press, p.176, as follows:

-   -   1. A piece of PVA-coated Septal Occluder made in accordance with        Example 1 is cut, weighed and measured;    -   2. Add 10 ml deionized water to the membrane and heat to 60° C.        in a tube block heater;    -   3. Add 0.1 gm of Cibachron Blue 3GA in 3 ml water, and heat at        60° C. for 30 min;    -   4. Add 1.5 gm NaCl and heat at 60° C. for 1 hr;    -   5. Raise the temperature to 80° C.;    -   6. Add 0.15 gm Na₂CO₃ and heat at 80° C. for 2 hr;    -   7. Cool, remove dye and rinse with water until no more color is        removed.

Controls not treated with PVA are wetted with absolute ethanol, thenwater-rinsed prior to the above regimen. Any residual color on controlscan be removed by a 15 min. treatment in absolute ethanol after waterrinsing, and followed by more water rinses. Alcohol will not affect thedye on the PVA.

Removal of the dye for quantification is done according to amodification of the procedure of Clonis, Y. D., Goldfinch, M. J., andLowe, C. R. Biochem. J. 197, 1981, 203-11, “The interaction of yeasthexokinase with Procion Green H-4G,” as follows:

-   -   1. The stained PVA-coated membrane is cut into small pieces and        placed in a vial containing 0.6 ml of 5N HCl. The vial is then        heated at 60° C. for 3 hrs in a test tube block heater.    -   2. Then, 2.4 ml of 2.5 M sodium phosphate buffer, pH 7.4, is        added, and the tubes are agitated for 5 min to extract the color        from the membrane pieces.    -   3. The extract is removed, and the absorbances are read on a        Varian DMS300 UV/VIS spectrophotometer at 620 nm.    -   4. The amount of dye in the extract is quantified from a        standard curve constructed by preparing a series of Cibachron        Blue solutions in the HCl/sodium phosphate mix ranging in        concentration from 20 to 200 μg/ml.    -   5. The membrane pieces from which the dye is extracted are        washed in water. These pieces should now be white.

The results are expressed as μg Cibachron Blue/mg device.

Four samples were tested according to the protocol above. The resultswere: 4.45+/−1.45 μg dye/mg Helex, N=4. The untreated (control) samplesdid not take up any dye.

Example 8 FTIR Test for Hydroxyl Groups

The degree of cross-linking of the layer may be assessed by FourierTransform Infrared Spectroscopy (FTIR). For example, with FTIR the freehydroxyl groups of polyvinyl alcohol (PVA) are detectable beforecrosslinking at approximately 3349 cm⁻¹. After cross-linking, the peakshifts to approximately 3383 cm⁻¹ and decreases in height. As a positiveinternal control, an FTIR peak at approximately 2942 cm⁻¹ due to the CH₂groups does not change position or height as a result of cross-linking.A shift in the hydroxyl group (—OH) peak position from approximately3349 cm⁻¹ to approximately 3383 cm⁻¹ with a decrease in peak height isan indication of the amount of PVA that has become cross-linked in theformation of the first layer.

The detection of the broad hydroxyl peak at approximately 3383 cm⁻¹ wasconfirmed on a HELEX Septal Occluder made according to Example 1, usinga Model 560ESP FTIR(NICOLET Corp., Madison, Wis.) and an ATR crystalapparatus (Zinc-Selenium 45 deg., Part #0050-603, SpectraTech, Stamford,Conn.). An untreated control HELEX Septal Occluder demonstrated no peakbetween 3000 and 3600 cm⁻¹.

Example 9 Evaluation of Tissue Ingrowth of Large Hole GORE-TEX®MYCROMESH® Biomaterial and GORE-TEX® DualMesh Biomaterial Impregnatedwith PVA

Six New Zealand White Rabbits were used in this study. Samples of LargeHole GORE-TEX® MYCROMESH® Biomaterial and GORE-TEX® DualMeshBiomaterial® were obtained from W. L. Gore & Associates, Inc.(Flagstaff, Ariz.). The samples were treated with PVA according to themethod described in Example 4 to create hydrophilic membranes. Foursamples were implanted in each of six animals. Two approximately 2.5 cmdisks, one MYCROMESH biomaterial and one DUALMESH biomaterial wereimplanted subcutaneously on the rabbit dorsum. Two approximately 3.75 cmdisks, one MYCROMESH biomaterial and one DUALMESH biomaterial wereimplanted intra-abdominally on the peritoneal wall in contact withviscera.

One side of both materials has a textured appearance. The MYCROMESHbiomaterial was implanted with the textured side opposed to muscle, theDUALMESH biomaterial was implanted with the textured side adjacent tomuscle. Animals were in-life for 7 and 30 days. There were 3 animals perin-life period.

Explant Observations

7 Day Explants:

No adhesions were observed to both materials in the intra-abdominalregions. Both materials were generally covered by a thin translucentcapsule within the subcutaneous tissue. The surrounding soft tissue wasunremarkable.

30 Day Explants:

No adhesions were observed to both materials. The surrounding softtissue in the intra-abdominal region appeared unremarkable. A thintranslucent capsule covered both implants in the subcutaneous region.

Histological Analysis

7 Day Explants:

Large Hole GORE-TEX® MYCROMESH® Biomaterial: The tissue response was aminimal foreign-body reaction with mild inflammation consistent withwound healing. The periimplant membrane consisted of early granulationtissue containing numerous and scattered large and small blood vessels.The cellular components, at the interface, consisted of histiocytes andforeign body giant cells. The peripheral nerve bundles appearedunremarkable with mild degeneration consistent with wound healing.Numerous blood vessels were observed within the macropores. Theneomesothelium dipped down and covered the macropores in theintraperitoneal region. Cellular migration into the interstices wasextensive and scattered throughout the implants.

Polarized light microscopy revealed the nodes of the expanded PTFE to bealigned parallel and consistent through the entire implant. The fiberlengths appeared large. Occasionally, the implants appeared looselyadherent to the underlying muscle tissue.

GORE-TEX® DUALMESH Biomaterial: The microstructure appeared similar tothe large hole MYCROMESH Biomaterial with consistent parallel alignednodes with large fibril lengths. Cellular migration into the intersticeswas extensive and scattered with numerous red blood cells andhistiocytes. The periimplant membrane consisted of granulation tissuewith numerous blood vessels. There was no evidence of bacteria orcalcification.

30 Day Explants:

Large Hole MYCROMESH® Biomaterial: The periimplant membrane appeared tohave a bland fibrocollagenous tissue with linearly aligned collagenfibers. The foreign-body tissue response was minimal. There was noevidence of inflammation in several of the implants. Cellular migrationinto the interstices was extensive with considerable collagendeposition. Blood vessels were numerous at the interface. The peripheralnerve bundles appeared unremarkable. Capillaries were observed withinthe interstices. Cellular migration was observed from both interfaces.There was no evidence of bacteria. A few microfoci of calcification wereobserved.

DUALMESH® Biomaterial:

The periimplant membrane consisted of a bland fibrocollagenous tissuewith aligned parallel collagen fibers to the interface. Theneomesothelial-like membrane appeared mature. Blood vessels werenumerous at the interface consisting predominantly of capillaries.Cellular migration into the interstices was extensive and oftenscattered. Collagen deposition was evident. Some of the suturesdemonstrated occasional microfoci of calcification. The foreign-bodytissue response was minimal. Several of the implants demonstrated noevidence of inflammation. There was no evidence of bacteria.

Conclusion

There was extensive cellular migration with collagen deposition into theinterstices of both implants at the 30 day time frame. The migration ofcells into both implants at the 7 day time frame was remarkable andconsiderable. The periimplant membrane appeared to consist of a blandfibrocollagenous tissue. Small blood vessels were numerous at theinterface of both implants. The nerve bundles in the subcutaneous site,at the 7 day time frame, demonstrated degeneration consistent with woundhealing, but appeared unremarkable at the 30 day time frame. Cellularingrowth into the treated membrane spanned the entire membrane width(>500 um).

Cellular migration into the interstices of the large hole MYCROMESH®Biomaterial was evident from both interfaces. The foreign-body tissueresponse was minimal. There was no evidence of inflammation in many ofthe implants at the 30 day time frame. There was no evidence of bacteriain all implants for all time frames. Occasionally, microfoci ofcalcification was sparsely observed in both implants and in the sutures.

Example 10 Subcutaneous Study of PRECLUDE® Dura Membrane in a RabbitModel

Six adult New Zealand White Rabbits were used in this study. Samples ofPRECLUDE® Dura Substitute were obtained from W. L. Gore & Associates,Inc. (Flagstaff, Ariz.) and treated according to the method described inExample 4 to create hydrophilic membranes. Two surfactants, DioctylSodium Sulfosuccinate (DSS) and Polyvinyl alcohol (PVA), were used torender the material immediately wettable with water or saline, allowingfor vessel and tissue visibility during surgery, and to help inpostoperative evaluations. Two, approximately 2.5 cm diameter disks wereimplanted subcutaneously on the dorsum of the rabbit. One device wastreated with DSS and one with PVA. There were two in-life periods, of 7days and 30 days, with 3 animals at each in-life time period.

Explant Observations

7 Day Explants:

All of the implants appeared wet-out and intact. The implants wereloosely adherent to the underlying muscle tissue. Occasional regions ofhemorrhage were observed at the suture site. The implants were coveredby a thin, translucent capsule along the anterior surface, toward theparietal region. Blood vessels were occasionally observed in theposterior region, along the muscle tissue.

30 Day Explants:

All of the implants were generally encapsulated by a translucent to aslightly opaque capsule. Many of the implants appeared to be firmly toloosely adherent to the underlying muscle tissue. Suture sites stillshowed persistent brownish/reddish granular regions.

Histological Evaluation

7 Day Explants:

A gradient effect was observed among all three materials. Consistently,the Dura Membrane treated with PVA revealed no adherence to theunderlying soft tissue. The adipose tissue, at the interface, appearedbenign. The foreign-body tissue response and histiocytic response wereminimal.

The Dura Membrane implants treated with DSS demonstrated no adherence tothe underlying muscle tissue. However, within the adipose tissuenumerous foreign body giant cells and histiocytes were observed with afew vacuoles. This adipose tissue appeared mildly inflamed.

The Dura Membrane control demonstrated a marked inflammatory effectcharacterized by a zone of fibrinous regions as well as histiocytes andforeign body giant cells within the adipose tissue. The periprosthetictissue was generally in close proximity to the Dura Membrane.

30 Day Explants:

The PRECLUDE® Dura Membrane implants treated with PVA consistentlyrevealed non-adherence to the underlying soft tissue. The periprosthetictissue appeared bland. The underlying adipose tissue was unremarkable.

The Dura Membrane implants treated with DSS demonstrated close proximityof the periprosthetic tissue to the surface of the Dura Membrane.Occasional regions of focal attachment were observed along one surfaceof the Dura Membrane. Generally, mild inflammation with hypercellularityof the periprosthetic tissue was observed. Occasional foreign body giantcells and histiocytes were observed within the adipose tissue.

The Dura Membrane control implants consistently revealed close proximityof the periprosthetic tissue to both surfaces of the implants. Numerousregions of focal attachment of the periprosthetic tissue to the DuraMembrane were observed. Generally, inflammation with hypercellularity ofthe periprosthetic tissue was observed. Foreign body giant cells andhistiocytes were observed within the adipose tissue. There was noevidence of bacteria or calcification at all time periods in all theimplants.

Conclusion

The PRECLUDE® Dura Membrane treated with PVA demonstrated non-adherenceof the periimplant membrane. The tissue response was bland.

The Dura Membrane treated with DSS demonstrated close proximity of theperiimplant membrane with focal regions of attachment and mildinflammation of the adipose tissue.

The Dura Membrane control implants demonstrated an adverse tissueresponse. This was characterized by close apposition of the periimplantmembrane to both surfaces. Numerous regions of focal tissue attachmentand persistent inflammation of the adipose tissue were apparent.

Example 11 Treatment of Corneal Prostheses

Corneal prostheses (or “keratoprostheses”) were made, treated with PVA,implanted and evaluated after explant. Shown in FIG. 12 is an isometricview of an implantable corneal prosthesis. Shown is a keratoprosthesis70 having expanded PTFE peripheral skirts 72, 74 attached to afluoropolymer corneal substitute 76. The expanded PTFE skirts weretreated with PVA in accordance with the procedure described in Example4. Shown in FIG. 13 is a cross-sectional view of an implantablekeratoprosthesis 70, showing a first expanded PTFE skirt layer 72, asecond expanded PTFE skirt layer 74 and an polymeric corneal substitutelayer 76. The corneal substitute layer 76 was shaped to conform tosurrounding native tissue and had a thickness and flexibility suitablefor long term ocular implantation. The corneal substitute layer 76provided an “internal” support frame for the expanded PTFE membranes.

Keratoprosthesis 70 was produced by providing a sheet of expanded PTFE,commercially available from W. L. Gore & Associates, Inc., as GORE-TEX®Soft Tissue Patch. The 2 mm (0.04″) thick expanded PTFE sheet was splitinto sheets approximately 0.15 mm (0.006″) thick. Holes having diametersof about 5.5 mm (0.22″) were laser cut into the sheets. A stackedassembly was then prepared for a first lamination process, which bondeda thermoplastic fluoropolymer elastomer to the laser cut sheet. Thestacked assembly was formed (from the top down) by aligning thefollowing layers: a first aluminum plate about 30 mm (0.12″) thick, asheet of KAPTON®, high temperature plastic about 0.05 mm (0.002″) thickavailable from E.I. duPont de Nemours, Wilmington Del., a sheet of 2 mmthick GORE-TEX® Soft Tissue Patch, a second sheet of KAPTON, a layer ofthermoplastic fluoropolymer elastomer about 0.2 mm (0.008″) thick, thelaser cut expanded PTFE sheet, a third sheet of KAPTON, a second sheetof 2 mm thick GORE-TEX® Soft Tissue Patch, a fourth layer of KAPTON anda second aluminum plate. All layers were about 10 cm (4″0) square. Thisstacked assembly was placed into a heated platen press and laminated atabout 200° C., under about 0.03 MPa (5 psi) for about 2 minutes. Thisfirst lamination process bonded the thermoplastic fluoropolymerelastomer to the first 0.15 mm thick expanded PTFE sheet with the lasercut holes.

A second sheet of the 0.15 mm thick expanded PTFE with laser cut holeswas then aligned to and bonded to the thermoplastic fluoropolymerelastomer. A stacked assembly was prepared for a second laminationprocess which bonded the thermoplastic fluoropolymer elastomer to thesecond laser cut sheet. The stacked assembly was formed (from the topdown) by aligning the following layers: a first aluminum plate about 30mm (0.12″) thick, a sheet of KAPTON, a sheet of 2 mm thick GORE-TEX®Soft Tissue Patch, a second sheet of KAPTON, a sheet of the 0.15 mmthick expanded PTFE with laser cut holes, the bonded thermoplasticfluoropolymer elastomer/first laser cut expanded PTFE sheet, a thirdsheet of KAPTON, a second sheet of 2 mm thick GORE-TEX® Soft TissuePatch, a fourth layer of KAPTON, and a second aluminum plate. All layerswere about 10 cm (4″) square. The laser cut holes in the first andsecond sheets were concentrically aligned to each other. This stackedassembly was placed into a heated platen press and laminated at about200° C., under about 0.03 MPa (5 psi) for about 2 minutes. This secondlamination process bonded the thermoplastic fluoropolymer elastomer tothe second 0.15 mm thick expanded PTFE sheet with the laser cut holes,resulting in a three layer laminate as depicted in FIG. 13.

The three layered laminate was then aligned onto a laser. Disksapproximately 9.7 mm (0.39″) were concentrically cut relative to theexisting 5.5 mm holes. The disks were then formed into the convex shapeby compression forming and then heating to retain the final shape. Theresulting keratoprosthesis is depicted in FIGS. 12 and 13.

The keratoprosthesis was then treated with PVA using the followingprocess:

-   -   1) The keratoprosthesis was placed into a 60 ml syringe        containing about 30 ml of 100% isopropyl alcohol. The air was        expelled from the syringe. The syringe plunger was then        partially withdrawn with the syringe port plugged, forming a        partial vacuum within the syringe. The vacuum was maintained for        about 15 seconds and then the plunger was allowed to relax. This        vacuum application was repeated five more times. The vacuum        application forced the residual air from the porous expanded        PTFE, allowing the alcohol to fully penetrate.    -   2) The keratoprosthesis was then soaked in a 2% PVA/DI water        solution for about 2 hours, stirring at about 45 minute        intervals.    -   3) The keratoprosthesis was then rinsed in DI water for about 30        minutes with occasional stirring.    -   4) The keratoprosthesis was then placed in a 2%        glutaraldehyde/1% hydrochloric acid-DI water solution for about        1.5 hours, with occasional stirring.    -   5) The keratoprosthesis was then rinsed in DI water for about 30        minutes with occasional stirring.    -   6) The treated keratoprosthesis was then sterilized prior to        implantation.

A study was performed to evaluate the healing process and tissueresponse of keratoprosthesis prototypes in a New Zealand White Rabbit.PVA treated e-PTFE keratoprostheses were compared with untreatedexpanded PTFE prototypes in four animals each. The groups were examinedby gross and histological analysis after an implant period of 90 days.

Prototypes treated with PVA had superior performance compared to theiruntreated counterparts. One prototype in the untreated group failed at68 days. Two of the four of the untreated group had skirt lifting,indicating poor device anchorage. Additional gross observations of theuntreated prototypes included patchy areas of wet-out expanded PTFEcompared with complete wetting-out of the expanded PTFE in the PVAtreated group. In addition, there was glistening on the anteriorexpanded PTFE surface of the PVA group, confirmed to be cornealepithelial attachment with histology. This phenomenon did not appear inthe untreated group. Tissue attachment in both groups stopped at theexpanded PTFE/thermoplastic elastomer junction.

While particular embodiments of the present invention have beenillustrated and described herein, the present invention should not belimited to such illustrations and descriptions. It should be apparentthat changes and modifications may be incorporated and embodied as partof the present invention within the scope of the following claims.

The invention claimed is:
 1. A device for implantation comprising aporous membrane supported by a support frame forming an implantabledevice; the porous membrane containing a hydrophilic substance adaptedto rapidly wet-out the porous membrane upon contact with an aqueoussolution.
 2. The device of claim 1 wherein the device is configured forcardiovascular implantation.
 3. The device of claim 1 wherein wet-outoccurs within 5 seconds of immersion in an aqueous solution.
 4. Thedevice of claim 3 wherein the aqueous solution comprises DI water. 5.The device of claim 3 wherein the aqueous solution comprises humanblood.
 6. The device of claim 1 wherein the porous membrane comprises anexpanded polytetrafluoroethylene.
 7. The device of claim 6 wherein thehydrophilic substance comprises polyvinyl alcohol (PVA).
 8. The deviceof claim 7 wherein the PVA is cross-linked in place.
 9. The device ofclaim 7 wherein wet-out occurs within 5 seconds of immersion in anaqueous solution.
 10. The device of claim 1 wherein the hydrophilicsubstance comprises polyvinyl alcohol (PVA).
 11. The device of claim 1wherein the PVA is cross-linked in place.
 12. The device of claim 10wherein wet-out occurs within 5 seconds of immersion in an aqueoussolution.
 13. The device of claim 1 wherein the device is configured toserve as a septal defect closure device.
 14. The device of claim 1wherein the device is configured to serve as a stent-graft.
 15. Thedevice of claim 1 wherein the device is configured to serve as anembolic filter.
 16. The device of claim 1 wherein the device iseffectively transparent to ultrasound imaging.